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December 21, 2005
By
Sahar Bedrood
B.S. and Asher Kimchi M.D.
Gdansk, Poland - Unfavorable metabolic changes and
impaired endothelial function in diabetic patients
make them more susceptible to post-operative
complications in cardiopulmonary bypass coronary
surgery (CPB). It has been shown that carnitine
administration in such patients can improve cardiac
metabolism and function in ischemic patients.
Suggested mechanisms include an increase in glucose
metabolism and reduction of toxic effects of
long-chain acyl-Co-A. Romauld Lango et al from the
Medical University Gdansk, Poland evaluated
hemodynamic changes associated with pre-operative
propionyl-L carnitine and L-carnitine administration
and its association with biochemical markers of
cardiovascular function. Their study, published in
the December 2005 issue of Cardiovascular Drugs
and Therapy indicates a significant improvement
of hemodynamics following propionyl-L carnitine
administration in diabetic patients undergoing
coronary-artery bypass grafting (CABG).
Sixty-eight diabetic patients undergoing
cardiopulmonary bypass coronary operation were given
intravenously 20 mg/kg b.w. L-carnitine (LC),
24 mg/kg b.w. propionyl-L-carnitine (PC), or
placebo (Cont). Endothelin and nucleotide
metabolites were determined intraoperatively in
arterial and coronary sinus blood and heart
biopsies.
Cardiac index at 6 and 12 h after cardiopulmonary
bypass was significantly higher in PC (3.30 ± 0.12
and 3.47 ± 0.15 L/min/m2) as compared to
control (2.92 ± 0.13 and 2.91 ± 0.16 L/min/m2;
P = 0.04 and P = 0.01, respectively).
Mean pulmonary artery pressure was lower in PC at 6
(20.8 ± 0.91 mmHg) and 12 h (20.7 ± 0.81 mmHg) in
comparison to control (23.5 ± 0.75 and 23.4 ±
0.75 mmHg; P = 0.03 and P = 0.02,
respectively). Trans-cardiac endothelin difference
on reperfusion was higher in control (0.33 ± 0.26 pmol/L)
than in LC (−0.61 ± 0.24 pmol/L, P = 0.012)
and tended to be higher than in PC (−0.29 ± 0.17 pmol/L,
P = 0.056). Trans-cardiac hypoxanthine
difference after 10 min reperfusion was
significantly higher in control (6.22 ± 1.08 μmol/L)
in comparison to LC (3.17 ± 0.66 μmol/L, P =
0.025) and PC (2.36 ± 0.73 μmol/L, P =
0.006). Myocardial hypoxanthine concentration was
lowest in PC.
This study demonstrates that
propionyl-L-carnitine administration before CABG
significantly improved post-operative recovery in
early diabetic patients. The study noted
improvements in cardiac index, reduction in
pulmonary pressure, reduction in trans-cardiac
endothelin concentration and accelerated myocardial
hypoxanthine, a marker for disturbed myocardial
metabolism induced by ischemia, washout. L-carnitine
did not produce significant improvements in
cardiovascular metabolism, thereby indicating that a
specific formulation of carnitine is an important
factor for future therapy.
Co-authors: Romuald Lango, Ryszard T. Smoleński,
Jan Rogowski, Janusz Siebert, Maria Wujtewicz,
Ewa M. Słomińska, Wiesława Łysiak-Szydłowska and
Magdi H. Yacoub
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